Leishmania Manipulation of Sand Fly Feeding Behavior Results in Enhanced Transmission

Abstract

In nature the prevalence of Leishmania infection in whole sand fly populations can be very low (<0.1%), even in areas of endemicity and high transmission. It has long since been assumed that the protozoan parasite Leishmania can manipulate the feeding behavior of its sand fly vector, thus enhancing transmission efficiency, but neither the way in which it does so nor the mechanisms behind such manipulation have been described. A key feature of parasite development in the sand fly gut is the secretion of a gel-like plug composed of filamentous proteophosphoglycan. Using both experimental and natural parasite–sand fly combinations we show that secretion of this gel is accompanied by differentiation of mammal-infective transmission stages. Further, Leishmania infection specifically causes an increase in vector biting persistence on mice (re-feeding after interruption) and also promotes feeding on multiple hosts. Both of these aspects of vector behavior were found to be finely tuned to the differentiation of parasite transmission stages in the sand fly gut. By experimentally accelerating the development rate of the parasites, we showed that Leishmania can optimize its transmission by inducing increased biting persistence only when infective stages are present. This crucial adaptive manipulation resulted in enhanced infection of experimental hosts. Thus, we demonstrate that behavioral manipulation of the infected vector provides a selective advantage to the parasite by significantly increasing transmission.

Author Summary

Leishmaniasis is a human parasitic disease that can result in destructive skin lesions or sometimes in fatal visceral involvement if left untreated. Infections are acquired via the bites of female sand flies, small blood-feeding insects. In this experimental study using mice, we show that Leishmania parasites can manipulate the behavior of sand flies so that infected flies become more tenacious, returning to feed if interrupted more readily and delivering more bites than uninfected flies. This change in behavior occurs only when the parasites have become infective to humans and are ready for transmission. At the same time, the parasites in the sand fly secrete a viscous gel that blocks up the gut and mouthparts and interferes with feeding. The result of this manipulation is an increase in the severity of disease and number of infections. These findings help us to better understand how human infection occurs, which is important when trying to devise ways of controlling this disease. It is currently estimated that at least 12 million people have leishmaniasis, with 2 million new infections every year.